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Biomedical subjects

A Kitahara

Publications and source records attributed to A Kitahara.

At least 19 recordsLinked to original sources

Malignant hyperthermia in a patient with Graves' disease during subtotal thyroidectomy.

We report the case of a 31-year-old man with Graves' disease who manifested malignant hyperthermia during subtotal thyroidectomy. His past medical history and family history were unremarkable. Before surgery, his condition was well controlled with propylthiouracil, beta-adrenergic blocker and iodine. During the operation, anesthesia was induced by intravenous injection of vecuronium and thiopental, followed by suxamethonium for endotracheal intubation. Anesthesia was maintained with nitrous oxide and sevoflurane. One hour after induction of anesthesia, his end tidal carbon dioxide concentration (ET(CO2)) increased from 40 to 50 mmHg, heart rate increased from 90 to 100 beats per min and body temperature began to rise at a rate of 0.3 degrees C per 15 min. Suspecting thyroid storm, propranolol 0.4 mg and methylprednisolone 1,500 mg were administered, which, however, had little effect. Despite the lack of muscular rigidity, the diagnosis of malignant hyperthermia was made based on respiratory acidosis. Sevoflurane was discontinued and dantrolene was given by intravenous bolus. Soon after the treatment, ET(CO2), heart rate and body temperature started to fall to normal levels. His laboratory findings showed abnormally elevated serum creatine phosphokinase and myoglobin but normal thyroid hormone levels. Since dantrolene is efficacious in thyrotoxic crisis and malignant hyperthermia, an immediate intravenous administration of dantrolene should be considered when a hypermetabolic state occurs during anesthesia in surgical treatment for a patient with Graves' disease.

Acidosis, Respiratory↗

Absorption in the visible region of YSZ implanted with Ag ions.

Ag ions were implanted into YSZ (yttrium-stabilized (cubic) zirconia) single crystals in two different energy regimes: kiloelectron volt and megaelectron volt. Optical absorption spectra were measured in the visible region at each stage in the annealing process of the sample. Depth profiles of Ag for the samples implanted at the energy of 20 keV were measured by X-ray photoelectron spectroscopy (XPS). For the samples implanted with Ag at the low energy of 20 keV, one large absorption peak appeared in the wavelength ranging from 470 to 536 nm, depending on the dose of Ag ions. As the sample was heated to 1000 degrees C, the intensity of the absorption peak decreased gradually, but a small, broad peak remains even at the temperature of 1000 degrees C. For the samples implanted with 2.8x10(16) Ag ion cm(-2) at the high energy of 3 MeV, one broad absorption peak was observed at around 470 nm. As the sample was heated sequentially to high temperatures, the peak gradually decreased and almost disappeared at 400 degrees C. When the sample was further heated to even higher temperatures, the absorption peak at 514 nm reappeared at 1000 degrees C and grew with heating time.

Journal Article↗

A large Japanese family with Machado-Joseph disease: clinical and genetic analysis.

We report clinical and genetic studies on a large Japanese family with Machado-Joseph disease (MJD), in which various different clinical phenotypes were seen in the same family, i.e., cerebellar ataxia type, severe amyotrophy type, and young-onset parkinsonism type. In addition, patients with very mild symptoms (formes frustes) were encountered. The expansion of the CAG repeat at the MJD locus ranged from 64 to 71 in 7 affected and 4 presymptomatic individuals. In our family, no clear inverse correlation was noted between the length of CAG-expansion and the age of onset, or the clinical phenotypes. Hyporeflexia was a common manifestation seen in 5 patients. It has been reported that the presence of peripheral neuropathy in MJD is associated with smaller increase in the CAG repeats; findings in our family conform with this observation.

Adolescent↗

[Bartonellosis].

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Anti-Bacterial Agents↗

Difference in dominant negative activities between mutant thyroid hormone receptors alpha1 and beta1 with an identical truncation in the extreme carboxyl-terminal tau4 domain.

Although different expression patterns of thyroid hormone receptor (TR) alpha1 and beta1 have been reported, no essential distinction has been established in their functions. Unlike the TR beta gene, a mutation in the TR alpha1 gene has never been found in patients with resistance to thyroid hormone (RTH). Previously we found a mutant TR beta with an 11-carboxyl (C)-terminal amino acid truncation (betaF451X) in a girl with severe RTH. BetaF451X is a natural mutant with disruption of the transactivation domain, tau4, and it had very strong dominant negative activities. Based on the fact that the 46 amino acid sequence in the extreme C-terminal region is identical in TR alpha1 and TR beta, except for a C-terminal three amino acid extension of TR alpha1, we constructed a mutant TR alpha1 (alphaF397X) with the identical C-terminal truncation to betaF451X, to study functional differences between TR alpha1 and beta1. Both betaF451X and alphaF397X had negligible T3 binding and transcriptional activities even with 1 microM T3. The dominant negative activities of the mutant TRs were remarkable and T3 response element (TRE)-dependent. Co-expression of betaF451X decreased the CAT activity of either wild-type TR alpha1 or beta1 at 100 nM T3 by approximately 90% on the TRE-pal2 and 70% on DR4. AlphaF397X inhibited the transcriptional activities of both wild-type TR alpha1 and beta1 by approximately 50% on TRE-pal2 and by 60% on DR4. The dominant negative potency of betaF451X was significantly stronger than that of alphaF397X on the TRE-pal2, -DR4 and chicken lysozyme silencer F2, but similar on TRE-myosin heavy chain alpha and malic enzyme. No partiality for the TR subtypes was found in the dominant negative effects of betaF451X and alphaF397X. Co-expression with RXR enhanced the dominant negative effects of alphaF397X, but not of betaF451X. The results indicate that there are different dominant negative properties between alphaF397X and betaF451X, which are TRE-dependent, despite their identical C-terminal truncation. Deletion in the tau4 domain might affect the receptor structures of TR alpha1 and beta1 differently.

Animals↗

Alterations in the enzyme activity and protein contents of protein disulfide isomerase in rat tissues during fasting and refeeding.

Protein disulfide isomerase (PDI) is an enzyme that participates in the formation of disulfide bonds. It is also known to be the subunits of some enzymes and the membrane-associated thyroid hormone-binding protein. In this study, we measured the quantitative distribution of PDI protein in rat tissues and examined the relationship between protein level and enzyme activity in PDI during fasting and refeeding. Western blotting with specific anti-PDI antiserum detected the PDI protein band of 55 kd. Among several tissues, liver contained the largest amount of PDI protein, followed by kidney and fat, in which one-third to one-fourth of the hepatic PDI protein existed. The PDI protein band was also detected in heart and muscle. Fasting for 3 days decreased PDI protein levels in rat liver by 40%; control levels were recovered after 3 days of refeeding. The same change was observed in kidney. PDI activity, measured by the scrambled ribonuclease method, did not show the parallel alteration to PDI protein level in liver and kidney. Isomerase activity decreased to 50% of control values during fasting, but did not recover by refeeding. Thyroidal status did not affect either PDI protein level or isomerase activity. These findings show that fasting and refeeding affect PDI protein and enzyme activity, and that PDI protein level does not always reflect PDI activity.

Animals↗

High incidence of positive autoantibodies against thyroid peroxidase and thyroglobulin in patients with sarcoidosis.

OBJECTIVE: Although abnormalities of the humoral immune system, such as increased immunoglobulin production, are known in sarcoidosis, the relationship between sarcoidosis and autoimmune disorders in uncertain. We studied the incidence of thyroid autoantibodies and the prevalence of Hashimoto's thyroiditis in patients with sarcoidosis. PATIENTS AND MEASUREMENTS: Sixty-two patients with pulmonary sarcoidosis, diagnosed by a combination of clinical, radiographic and histological findings were studied. As controls, three groups of subjects aged 40 and over without a known history of thyroid disease (60 patients with pulmonary diseases other than sarcoidosis, 88 hospital employees and 82 company workers), were also analysed. Antibodies against thyroid peroxidase (TPO-Ab) and purified thyroglobulin (Tg-Ab) were measured by radioimmunoassay and antibodies against microsomal antigen (MCHA) and thyroglobulin (TGHA), by haemagglutination. RESULTS: Seventeen of 62 patients (27.4%) had either positive TPO-Ab or Tg-Ab or both. All the patients with positive thyroid autoantibodies were of middle or advanced age, and the incidence of positive TPO-Ab/Tg-Ab in patients with sarcoidosis aged 40 and over was 54.5% in males, 32.4% in females and 37.8% overall. The prevalence was significantly higher in males compared to age-matched control males (0-7.7% in the controls), and in female patients was twice that found in controls (11.8-16.3%). Seven patients had Hashimoto's thyroiditis, indicating that the prevalence was 11-3%, and much higher than that previously reported. CONCLUSIONS: The data show a remarkably high incidence of thyroid autoantibodies in patients of middle of advanced age with sarcoidosis, especially in males, and a higher prevalence of Hashimoto's thyroiditis than in previous reports.

Age Factors↗

Introducing a point mutation identified in a patient with pituitary resistance to thyroid hormone (Arg 338 to Trp) into other mutant thyroid hormone receptors weakens their dominant negative activities.

Clinical resistance to thyroid hormone (RTH) has been classified into generalized resistance to thyroid hormone (GRTH) and pituitary resistance to thyroid hormone (PRTH) types. Since similar mutations have been identified in tri-iodothyronine (T3) receptor (TR) beta gene in GRTH and PRTH, and since considerable overlap has been seen in the clinical manifestations in patients with GRTH and PRTH, two subtypes of RTH are now considered to be a continuous spectrum with the same genetic defect. A point mutation at amino acid Arg 338 to Trp (R338W) which we identified in a patient with PRTH is very interesting, since R338W has been found in several other patients with PRTH, raising the possibility that this mutation may tend to associate with a phenotype of PRTH. In our previous study, we found that R338W had relatively less impaired transcriptional potency, weaker dominant negative activity on various T3 response elements and poor homodimer formation, as compared with another GRTH mutant. In this study, to investigate the functional properties of R338W further, especially in terms of the relation between transcriptional activity and dimer formations, we introduced the R338W mutation into the mutant receptors, K443E and F451X, constructing the double mutants, R338W/K443E and R338W/ F451X. Both R338W/K443E and R338W/F451X showed negligible T3 binding and transcriptional activities. The dominant negative activities of K443E and F451X were, however, significantly weakened by introducing the R338W mutation. As a control, a double mutant G345R/K443E was constructed by introducing a point mutation, G345R, located in the same exon 9 as R338W, into the K443E mutant. Dominant negative activity did not differ between G345R/K443E and K443E. Homodimer formation was significantly reduced in the double mutants containing R338W, but not G345R. In summary, introducing the R338W mutation, but not G345R, into the mutant TR significantly weakened the dominant negative activity, despite further impairment of the T3 binding and transcriptional activities.

Cells, Cultured↗

Leukoencephalopathy induced by tegafur: serial studies of somatosensory evoked potentials and cerebrospinal fluid.

A case of leukoencephalopathy induced by tegafur, an antineoplastic derivative of 5-FU, is reported. The patient received 600 mg of tegafur p.o. for 16 days before excision of rectal cancer. After the operation, gait disturbance and mental abnormalities appeared. He became akinetic and mute within a few days following readministration of tegafur. Serial studies of brain CT, somatosensory evoked potentials (SEP) were made, and myelin basic proteins (MBP) in the cerebrospinal fluid were measured. The level of MBP was about twice the normal value and the central conduction time (CCT) of SEP was prolonged at admission. The value of MBP and CCT improved with recovery from akinetic mutism.

Akinetic Mutism↗

High idiotypic connectivity of the VH7183-encoded antibodies directed to a murine embryonic carbohydrate antigen, Lewis Y, as ascertained by syngenic anti-idiotype monoclonal antibodies.

The Lewis Y Ag is a carbohydrate Ag which is closely related to a well-known murine embryonic Ag, the stage-specific embryonic Ag-1 (SSEA-1), in its biochemical structure. It is expressed at the surface of murine embryonic cells as well as many murine cancer cells. For the analysis of idiotopes carried by the anti-Lewis Y antibodies, we generated two syngenic anti-idiotypic mAb, Id-A1 and Id-B4 (both BALB/c IgG1), which are directed to the idiotypic determinants carried by the anti-Lewis Y mAb, AH-6 (BALB/c IgM). Both Id-A1 and Id-B4 (Ab2) recognized paratope-related idiotopes carried by the AH-6 antibody (Ab1); they specifically inhibited the binding of AH-6 to the Lewis Y Ag. The high idiotypic connectivity of anti-Lewis Y antibodies was noted; the polyclonal anti-idiotype antibody, produced in the sera of BALB/c mice by immunizing AH-6 antibody, cross-reacted with several anti-Lewis Y mAb which has been established in different laboratories. Id-B4 and Id-A1 seem to represent such cross-reactive anti-idiotypic antibodies. Id-A1 recognized an idiotope carried by two out of six panel Ab1 mAb directed to the Lewis Y Ag. Id-B4 reacted with four out of the six panel antibodies, and was considered to recognize a recurrent idiotope of anti-Lewis Y antibodies which occurs more commonly than the idiotope recognized by Id-A1. All of the anti-Lewis Y antibodies which carry idiotopes that react with Id-A1 or Id-B4 were encoded by the VH genes of the VH7183 family; the most D-J proximal VH gene family in BALB/c mice, which is known to be preferentially expressed in embryonic B cells. Immunization of BALB/c mice with keyhole limpet hemocyanin-conjugated Id-B4 and/or Id-A1 induced a significant titer of anti-Lewis Y antibodies (Ab1-like Ab3) in the sera.

Animals↗

Quantitative and qualitative characterization of human cancer-associated serum glycoprotein antigens expressing epitopes consisting of sialyl or sialyl-fucosyl type 1 chain.

The levels of carbohydrate antigens having epitopes consisting of type 1 chain (R----Gal beta 1----GlcNAc beta 1----3Gal beta 1----R) in the sera of patients with various malignant and nonmalignant disorders have been investigated with the use of three monoclonal antibodies, N-19-9, FH-7, and FH-9. Serum levels of 2----3 sialylated Lea antigen and 2----6 sialylated Lea antigen, defined respectively by antibodies N-19-9 and FH-7, were found to be frequently high in patients with cancer of the digestive system, particularly pancreatic cancer. High levels of 2----3,2----6 disialylated Lc4 antigen, defined by antibody FH-9, were less frequent in cancer patients when compared with the other two antigens. In patients with nonmalignant disorders, especially renal and autoimmune diseases, serum levels of the two type 1 chain antigens defined by FH-7 and FH-9 were more frequently high than that defined by N-19-9. Molecular weights and other general biochemical characteristics of serum mucin carrying the type 1 chain determinants were not significantly different in cancer patients as compared with patients with nonmalignant disorders. However, the degree of glycosylation of the antigen, as assessed by its solubility in perchloric acid, showed significant differences; i.e., the mucin antigen carrying 2----6 sialylated Lea determinant in the sera of patients with nonmalignant disorders had the highest carbohydrate/protein ratio, followed by the mucin carrying the same determinant in the sera of cancer patients. Mucin antigen carrying 2----3 sialylated Lea antigen or 2----3, 2----6 disialylated Lc4 antigen in cancer patients had the lowest carbohydrate/protein ratio among the four groups tested. Thus, the carbohydrate/protein ratio in the type 1 chain mucin antigens in sera of normal subjects is higher than that in sera of cancer patients (P less than 0.05). This finding is in contrast to previous findings on the mucin antigens carrying the type 2 chain determinant (R. Kannagi et al., Cancer Res., 46: 2619-2626, 1986), in which the mucin antigen in cancer patients was found to have a much higher carbohydrate/protein ratio than that carrying the same antigenic determinants in patients with nonmalignant disorders.

Antibodies, Monoclonal↗

Fucosylated type-2 chain polylactosamine antigens in human lung cancer.

Four specific monoclonal antibodies (MAbs) have been used to study distributions of fucosylated type-2 chain polylactosamine antigens, Lex, poly Lex, Ley and sialylated Lex-i antigens, in human lung cancer tissues and in the serum of patients with lung cancers. Radioimmunoassay frequently showed abnormally high antigen levels in the sera of 66 lung cancer patients tested. When histological typing was performed, high serum levels of the above 4 antigens were most frequently observed in patients with adenocarcinoma of the lung; i.e., after combining the results from the 4 antigens, 75% of the sera from patients with lung adenocarcinoma were positive (50% in the case of large-cell carcinoma, 30% in the case of squamous-cell carcinoma and 27% for small-cell carcinoma). Among the 4 antigens, the sialylated Lex-i antigen had the highest positive incidence, 58%, in the sera of patients with adenocarcinoma of the lung, compared to 33% for Ley, 29% for poly Lex, and 8% for Lex antigen. On the other hand, when the distributions of these antigens in the lung cancer tissues of 42 patients were studied by immunohistological techniques, the Ley antigen had the highest positive incidence, 100%, in lung adenocarcinoma tissues, poly Lex antigen had 86%, sialylated Lex-i antigen had 71%, and Lex antigen had 29%. In cancer tissues, the incidence of non-sialylated antigens, such as Ley, poly Lex and Lex antigens, often exceeds the positive incidence of the sialylated antigen, but the sialylated form of the antigen, such as sialylated Lex-i antigen, appears more often than the non-sialylated form in patients' sera.

Adenocarcinoma↗

Significance of 2-3 and 2-6 sialylation of Lewis a antigen in pancreas cancer.

Distributions of sialylated derivatives of Lewis a (Lea) antigen in cancer tissue of the human pancreas and in the sera of patients with pancreas diseases have been studied; the significance of 2-3 and 2-6 sialylation of Lea antigens in pancreas cancer have been investigated using specific monoclonal antibodies. In most pancreas cancer tissue the 2-3 sialylated Lea antigen was found to be specifically distributed in cancer cells as determined by immunohistologic techniques, while a significantly smaller amount of the antigen was detected in surrounding nonmalignant pancreas tissue, which was infiltrated by cancer cells. Conversely, the 2-6 sialylated Lea antigen was abundantly present in nonmalignant pancreas tissue, while it was less frequently present in pancreas cancer cells. When the sera of 66 patients with pancreas diseases were examined for these sialylated Lea antigens, correlation studies showed that the levels of 2-3 sialylated Lea tended to be 44.1 times more than the levels of 2-6 sialylated Lea in the sera of cancer patients. The average ratio of 2-3 sialylated Lea to 2-6 sialylated Lea was 0.23 in the sera of patients with pancreatitis. These data collectively indicate that the 2-3 sialylation of Lea is remarkably enhanced, and the 2-6 sialylation of Lea antigen is suppressed in pancreas cancer. The determination of the 2-3 sialylated Lea to 2-6 sialylated Lea ratio in patients with pancreas diseases may be helpful for the differential diagnosis of pancreas cancer and nonmalignant pancreatic disorders.

Antibodies, Monoclonal↗

On the factors influencing the dispersion of radioiodines.

Radioactivities dispersed from 0.1 N sodium hydroxide solutions of 123I, 125I, or 131I were measured, and the factors influencing dispersion of radioiodines were analyzed. The radioiodines dispersed were trapped by glass fiber filters, charcoal filters, and separable paint. The factors influencing the dispersion of radioiodines are discussed in terms of the dispersal rate, which defined as the ratio of total activity of three kinds of traps in a unit time to whole activity. In order to clarify the factors influencing the dispersal rate, we carried out the experiments; on the effect of reducing agent, that of radioactive concentration of radioiodine, that of mixing the 125I solution with 131I, and that of scavenging hydrated electrons and hydroxyl radicals. It could be concluded from experimental results that the principal factors influencing dispersion of radioiodines are the number of atoms of radioiodine per volume and the energy absorbed in solution from radioiodines. In regard to the absorbed energy, we thought that the dispersion of radioiodines is influenced mainly by hydrated electron, not markedly by hydroxyl radical.

Iodine Radioisotopes↗

Distribution of calpains and calpastatin in human blood cells.

The occurrence and molecular sizes of calpains and calpastatin in the lysates of human erythrocytes, platelets, lymphocytes/monocytes, and polymorphonuclear cells were studied by immunoelectrophoretic blot analysis. The basic uniformity among these cells of the 85-kDa and 83-kDa heavy subunits of low- and high-Ca2+-requiring calpains I and II, respectively, and of the 29-kDa light subunit was confirmed. Molecular diversity of calpastatin species, ranging from 70 kDa to 107 kDa, among different blood cells was also shown. The obtained data are consistent with those known for other animal tissues, thus settling hitherto uncertain or rather controversial issues on the distribution of calpains and calpastatin in human blood cells.

Blood Platelets↗

Platelet factor XIII is activated by calpain.

The action of calpain (EC 3.4.22.17; Ca2+-dependent cysteine proteinase) on platelet factor XIII has been studied. Calpain I activated platelet factor XIII up to 76% of the maximum level observed with thrombin. Activation was accompanied by the limited proteolysis of the a subunit of platelet factor XIII to produce a 76 kDa fragment which was comparable to the proteolytic product by thrombin. Activation of platelet factor XIII by calpain was inhibited by EDTA, leupeptin, and endogenous calpain-specific inhibitor calpastatin. These findings suggest that calpain is responsible for the intracellular activation of platelet factor XIII.

Blood Platelets↗

Specific localization of tissue-type transglutaminase in adrenocorticotropin-producing cells of the human pituitary gland as demonstrated by immunohistochemistry.

The distribution of transglutaminases, the Ca2+-dependent protein cross-linking enzymes, in the human pituitary gland was investigated by immunohistological methods using specific antibodies. Tissue-type transglutaminase was specifically localized in ACTH-producing cells, and the cells producing GH, PRL, TSH, FSH, and LH contained no appreciable amount of the enzyme. No detectable plasma-type transglutaminase (coagulation factor XIII) was found in pituitary tissue. In a previous study we demonstrated that ACTH-producing cells contain very little Ca2+-dependent proteinases (calpain), but a remarkable amount of their inhibitor, calpastatin. Pituitary gland cells producing hormones other than ACTH contained calpains, but no detectable calpastatin. These results collectively suggest that intracellular substrate proteins in ACTH-producing cells are protected from Ca2+-dependent degradation and are substrates for Ca2+-dependent cross-linking catalyzed by the tissue-type transglutaminase. In other pituitary gland cells, conversely, the intracellular substrate proteins are more likely to undergo Ca2+-dependent degradation than cross-linking.

Adolescent↗